Protective effects of salusin-α and salusin-ß on renal ischemia/reperfusion damage and their levels in ischemic acute renal failure.

Salusin-α and salusin-ß are expressed in many tissues including the central nervous system, vessels and kidneys; they have been shown to decrease endoplasmic reticulum stress during heart ischemia/reperfusion (I/R) and to decrease apoptosis. We investigated the relation of salusin-α and salusin-ß levels to acute ischemic renal failure. We also investigated whether these peptides are protective against renal I/R damage. Fifty-three rats were divided into six groups: control, I/R, I/R + salusin-α1, I/R + salusin-α10, I/R + salusin-ß1 and I/R + salusin-ß10. After removing the right kidney, the left kidney was subjected to ischemia for 1 h and reperfusion for 23 h. The treatment groups were injected subcutaneously at the beginning of ischemia with 1 or 10 µg/kg salusin-α, and 1 or 10 µg/kg salusin-ß. Histopathology was assessed at the end of the experiment. Superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-PX) activity and malondialdehyde (MDA) levels were measured in the kidney tissue. Serum levels of blood urea nitrogen (BUN), creatinine (Cre), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and interleukin-1 beta (IL-1ß) also were measured. Levels of salusin-α and salusin-ß were measured in the serum and kidney tissues of the control and I/R groups. SOD, CAT and GSH-PX activities were decreased and the levels of MDA, TNF-α, IL-6, IL-1ß, BUN and Cre were increased in the I/R group compared to controls. Severe glomerular and tubular damage was apparent in the I/R group compared to controls. The level of salusin-ß was decreased in the serum and kidney tissue of the I/R group compared to controls, whereas the level of salusin-α was decreased in the serum and increased in the kidney tissue. Salusin-α and salusin-ß administration increased SOD and GSH-PX enzyme activation and decreased the levels of MDA, TNF-α, IL-6 and IL-1ß compared to the I/R group. BUN and Cre levels were decreased in the I/R + salusin-α1 group and the level of Cre was decreased in I/R + salusin-ß10 group compared to the I/R group. We demonstrated a protective effect of salusin-α and salusin-ß against renal I/R damage. Changes in the levels of salusin-α and salusin-ß in the I/R group suggest that these peptides may be associated with acute renal failure.

Proximal protection with hybrid stent, a safer combination for carotid artery stenting against carotid endarterectomy?

AIM: Carotid revascularization is an established theurapeutic modality in preventing stroke and death among patients with severe carotid stenosis. Although carotid endarterectomy remains as the primary option, carotid stenting is accepted as an alternative for patients with high risk for carotid endarterectomy. Recently published reports have better results with proximal protection devices when compared with distal protection devices. These studies have revealed less microembolic signals and less periprocedural new ischemic lesions on diffusion weighted magnetic resonance imaging. Stent choice may be also important for these procedures as open cell stent design has advantage of better flexibility whereas closed cell systems have an advantage of better scaffolding. Hybrid stents which are composed of open cells in the proximal and distal part and closed cells in the middle may carry both advantages. The aim of this study is to demonstrate whether combination of proximal protection devices with hybrid stents can be a safe alternative for carotid stenting in terms of periprocedural and 30-day outcomes. METHODS: Here we retrospectively evaluated 68 symptomatic carotid stenosis patients undergoing carotid stenting with hybrid stent (Cristallo Ideale®, Invatec s.r.l., Medtronic, Italy) and proximal protection device (MO.MA®, Invatec s.r.l., Medtronic, Italy). RESULTS: Our results showed only 1 minor stroke in the periprocedural period and during the first 30-day after stenting, with no death or myocardial infarction. CONCLUSION: Although our case number is not large, we propose that carotid stenting may be safer with utilization of proximal protection system and hybrid type carotid stents.

A patient presenting with concha bullosa in another concha bullosa: a case report.

INTRODUCTION: Anatomic variations of the paranasal sinuses are very common. The paranasal sinus anatomy should be carefully examined prior to performing endoscopic sinus surgery in terms of both existent pathologies and anatomic variations. The anatomy of the paranasal sinuses and its variations have gained importance, along with advances in coronal paranasal sinus computed tomography and extensive use of endoscopic sinus surgery. CASE PRESENTATION: A 53-year-old Caucasian woman was admitted to our clinic with complaints of nasal breathing difficulties and headache persisting for a long time. Another concha bullosa was detected in the middle concha bullosa on preoperative paranasal computed tomography examination. It is known that the paranasal sinuses have a number of anatomical variations. CONCLUSION: Herein we report a rare case, along with a review of the literature, to emphasize that a concha bullosa inside another concha bullosa should not be ignored.

Early outcomes of carotid artery stenting.

BACKGROUND AND AIM: Ischemic cerebrovascular events are the most common reason for patients to be bedridden and the third most common reason for death. Many studies in recent years have demonstrated that carotid artery stenting (CAS) may be an alternative to carotid endarterectomy (CEA). In this study, we aimed to report early outcomes of patients who were treated with CAS in our clinic and discuss practicability, advantages and safety of CAS. METHODS AND FINDINGS: Eighty patients who underwent CAS between December 2009 and May 2011 were eligible. The mean age was 65 years (range, 49 - 89 years). Of the study group, 73.75% were males and 26.25% were female. The percentage of asymptomatic patients was 11.7%, and the remaining patients were symptomatic. A distal embolic protection device (Angioguard®) was used in 22% of the patients whereas, in the other patients (78%), a proximal blockage system (Mo.MA®) was used. Self-expandable hybrid stents were implanted in all patients and post-dilatation was performed after implantation. None of the patients suffered from stroke, myocardial infarction or death due to CAS during their hospital stay. The mean follow-up period was 10 months (range 2 - 18 months) after discharge. None of the patients had died or had a stroke, a transient ischemic attack (TIA), or a myocardial infarction during the follow-up period. Re-stenosis was not observed in the follow-up carotid Doppler ultrasonography; flow rates were within normal limits. CONCLUSION: No major complication was observed during the early follow-up period in patients who underwent CAS in our clinic. Only 2 (2.5%) patients showed transient numbness and weakness and these did not lead to morbidity. In the management guide of extracranial carotid and vertebral artery diseases, CAS, in the light of recent studies, is recommended as an alternative to CEA in recommendations for revascularization. One of the important issues emphasized in this guide is the experience of centers. Very low complication rates after CAS suggested that, with suitable patient selection and an experienced team, similar results may be obtained.

An overview on natural cholinesterase inhibitors--a multi-targeted drug class--and their mass production.

Cholinesterase enzyme family consisting of acetylcholinesterase (AChE) and butrylcholinesterase (BChE) is important in pathogenesis of Alzheimer's disease (AD), explained by "cholinergic hypothesis". Accordingly, deficiency of the neuromediator called "acetylcholine" excessive amount of BChE has been well-described in the brains of AD patients. Consequently, cholinesterase inhibition has become one of the most-prescribed treatment strategies for AD. In fact, cholinesterase inhibitors have been also reported for their effectiveness in some other diseases including glaucoma, myasthenia gravies, as well as Down syndrome, lately. They play a role in the action of mechanism of insecticidal drugs such as carbamate derivatives as well as nerve gases such as malathion and parathion. All these utilizations can make them a multi-targeted drug class putting a special emphasis on AD therapy in the first place. Several inhibitors of cholinesterases with synthetic and natural origins are available in drug market; however, the reasons including side effects, relatively low bioavailability, etc. limit their uses in medicine and there is still a great demand to discover new cholinesterase inhibitors. Galanthamine, an alkaloid derivative isolated from snowdrop (Galanthus nivalis L.), is the latest anticholinesterase drug used against AD. Huperzine A, isolated from Huperzia serrata (Thunb.) Trev. is the most-promising drug candidate with potent anticholinesterase effect and it is a licensed anti-AD drug in China. In this review, a short introduction will be given on known cholinesterase inhibitors and, then, galanthamine and huperzine A will be covered in regard with their cholinesterase inhibitory potentials and mass productions by organic synthesis and in vitro culture techniques.

Extraordinary pathologic entities within the concha bullosa.

OBJECTIVE: To retrospectively analyze the extraordinary pathologic entities inside the concha bullosa (CB). METHODS: Surgical interventions were performed on 136 patients (234 CB) at the Department of Ear, Nose, and Throat, and Head and Neck Surgery, Izmir Tepecik Training and Research Hospital, Izmir, Turkey between January 2002 and December 2007. Radiological and histopathological findings of these cases were reviewed retrospectively. RESULTS: In 203 (86.8%) of the 234 cases, only a pneumatized cavity was observed. The cavity was filled with purulent secretion in 13 (5.6%) cases. A bony septum, pyocele, polyp, ossifying fibroma, fungus ball, and cholesteatoma were the other extraordinary pathologies associated with CB. CONCLUSION: Although most of the CB cases have pneumatized cavity, it should be kept in mind that some extraordinary pathologies can be associated with CB.

Urinary dysfunction in multiple sclerosis.

We aimed to determine the prevalence of urinary symptoms and complications in multiple sclerosis (MS) and to investigate the correlation of these symptoms and complications with urodynamic findings and disease characteristics (primary progressive, relapsing-remitting and secondary progressive). Fifty-two patients with MS were enrolled in the study. Patients were divided into three clinical types: primary progressive, relapsing-remitting and secondary progressive. Urological symptoms and complications were recorded. Each patient underwent a urodynamic investigation. Patients were evaluated for overall disability using the Expanded Disability Status Scale (EDSS). We found that 22 patients had primary progressive, 18 patients had relapsing-remitting and 12 patients had secondary progressive MS. Urgency was the most frequent urinary symptom (65%). Urinary infection was the most frequent urinary complication (15%). Detrusor hyperreflexia was found to be the main bladder dysfunction (27%). Detrusor sphincter dyssynergia was found in 25% of patients, and detrusor hyporeflexia was detected in 6%. No relationship was found between urinary symptoms and urodynamic abnormalities (p>0.05) and between urinary complications and urodynamic findings (p>0.05). No significant correlation was found between disease characteristics and urinary symptoms, urinary complications or urodynamic findings (p>0.05). We suggest that the assessment of urological symptoms and urodynamic evaluation is critical for evaluating quality of life in MS.

Surgery of carotid body tumour: 14 cases in 7 years.

OBJECTIVE: The goal was to review our experience in the management of carotid body tumours. MATERIAL AND METHODS: A retrospective study was performed of patients in whom carotid body tumour was diagnosed between 1998 and 2005. Data were retrieved from hospital discharge files. RESULTS: Fourteen patients were operated on. There were five patients in Shamblin class I, 4 in class II, and 5 in class III. Duplex examination was performed in all patients. Computerized tomography scans were performed in eight (57%) patients and magnetic resonance imaging scans in five patients (36%). Angiography was performed in all patients, preoperative embolization was attempted in 5 (36%). The blood loss for these patients was not less than for those without embolization. Three patients (21%) had postoperative cranial nerve deficits. All the deficits resolved. The internal carotid artery was injured in two patients and the external carotid artery was injured in three patients (36%). No stroke occured. CONCLUSION: Surgical resection is the treatment of choice for carotid body tumours. Observation of these tumours is not recommended because progressive growth is associated with increased risk of neurological deficits. Early surgical management is recommended to avoid neurological deficit due to a Shamblin class III tumour. We also do not recommend embolization.

[Surgery of cardiac hydatid cysts. Experience of 39 years]. / Chirurgie des kystes hydatiques cardiaques. Trente-neuf ans d'expérience.

In some countries, Hydatidosis is a common public health problem but cardiac hydatid cysts are rarely observed. The evaluations of operative results and follow up of cardiac hydatid cases. Twenty-five consecutive unselected patients suffering from cardiac hydatidosis and operated on between 1967 and 2006 in Siyami Ersek Cardiothoracic and Vascular Surgery Center were retrospectively analyzed. In 10 of these patients the hydatid cyst was intracardiac, while in 13 patients cysts were extracavitary but located into the pericardium. In 2 patients the hydatid cyst was both intra and extracavitary. Mean age of the patients was 31+/-9.2. The female/male ratio was 17/8. The 12 patients with intracavitary and 2 patients wit extracavitary hydatid cysts were operated on with the aid of extracorporeal circulation. One patient died postoperatively. In one patient recurrence of the hydatidosis was observed. The majority of cases in previous publications were located in the left side of the heart. In our series, most were located in the right heart. In such cases clamping the pulmonary artery is mandatory to prevent pulmonary migration. Careful resection is important for prevention of recurrence.

Effects of the integrin-linked kinase inhibitor QLT0267 on squamous cell carcinoma of the head and neck.

OBJECTIVE: To study the expression of integrin-linked kinase (ILK) in human squamous cell carcinoma of the head and neck (SCCHN) tumor specimens and cell lines and the efficacy of the novel small molecule QLT0267. DESIGN: Immunohistochemical analysis of 17 SCCHN tumor tissue specimens and 3 normal tongue tissue specimens for ILK expression and in vitro analysis of the effectiveness of QLT0267 on SCCHN cells. SETTING: Academic medical center. MAIN OUTCOME MEASURES: Expression levels of ILK in SCCHN tumor specimens and cell lines and the efficacy of QLT0267 in inhibiting cell growth and inducing apoptosis in SCCHN cell lines. RESULTS: Most SCCHN tumor specimens stained for ILK, whereas none of the 3 normal tongue tissue specimens stained for ILK. Integrin-linked kinase was expressed in all 6 SCCHN cell lines tested. In 4 pairs of normal and SCCHN tumor specimens, ILK expression and activity were higher in most tumor samples tested. A kinase assay showed that QLT0267 inhibited the ILK activity of 2 SCCHN cell lines (TU167 and MDA1986). Modified tetrazolium salt 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, DNA fragmentation ladder, and TUNEL (terminal deoxynucleotidyl transferase-mediated biotin-deoxyuridine triphosphate nick-end()labeling) assays showed that QLT0267 inhibited cell growth and induced apoptosis in these 2 cell lines. A dose-dependent decrease in Akt phosphorylation was observed for these 2 cell lines on treatment with QLT0267. CONCLUSIONS: Integrin-linked kinase is overexpressed in SCCHN tumor specimens. Targeting ILK with the small-molecule ILK inhibitor QLT0267 inhibits cell growth and induces apoptosis in SCCHN cell lines by reducing ILK activity and Akt phosphorylation. Integrin-linked kinase may be an attractive target for molecular therapy with which to enhance treatment of SCCHN.

Integrin-linked kinase is a potential therapeutic target for anaplastic thyroid cancer.

We investigated integrin-linked kinase (ILK), a focal adhesion serine-threonine protein kinase, as a new molecular target for treating anaplastic thyroid cancer. ILK mediates cell growth and survival signals and is overexpressed in a number of cancers. Therefore, we hypothesized that inhibition of ILK leads to growth arrest and apoptosis of thyroid cancer cells. According to Western blotting, the level of ILK protein was highly expressed in one papillary (NPA187) and four of five (Hth74, DRO, ARO, KAT4, and K4) anaplastic thyroid cancer cell lines. Immunohistochemical analysis of a human tissue microarray revealed that ILK was highly expressed in anaplastic thyroid cancer but not in normal human thyroid tissue. Treating thyroid cancer cell lines with a new ILK inhibitor, QLT0267, inhibited epidermal growth factor-induced phosphorylation of AKT, inhibited cell growth, and induced apoptosis in the NPA187, DRO, and K4 cell lines. QLT0267 also inhibited the kinase activity of immunoprecipitated ILK in four of five cell lines. Tumor volumes in mice treated with QLT0267 were significantly reduced compared with those in untreated mice. In immunohistochemical studies, QLT0267 suppressed phosphorylated p-AKT and angiogenesis (i.e., reduced mean vascular density) and induced apoptosis in both tumor cells and tumor-associated endothelial cells of the thyroid DRO xenografts. In summary, we found that ILK expression and activity were elevated in human anaplastic thyroid cancer and ILK inhibition led to growth arrest and apoptosis in vitro and in vivo. Our results provide preliminary evidence that ILK is a potential therapeutic target for treating anaplastic thyroid cancer.

Targeted molecular therapy of anaplastic thyroid carcinoma with AEE788.

Anaplastic thyroid carcinoma (ATC) is one of the most aggressive human malignancies with a mean survival of only 6 months. The poor prognosis of patients with ATC reflects the current lack of curative therapeutic options and the need for development of novel therapeutic strategies. In this study, we report the results of a preclinical study of AEE788, a dual inhibitor of epidermal growth factor receptor (EGFR) and vascular endothelial growth factor receptor (VEGFR) tyrosine kinases, against ATC. AEE788 was able to inhibit the proliferation and induce apoptosis of ATC cell lines in vitro. Administration of AEE788, alone and in combination with paclitaxel, to athymic nude mice bearing s.c. ATC xenografts inhibited the growth of ATC xenografts by 44% and 69%, respectively, compared with the control group. Furthermore, tumors from mice treated with AEE788, alone and in combination with paclitaxel, showed increase in apoptosis of tumor cells by approximately 6- and 8-fold, respectively, compared with the control group. The microvessel density within the ATC xenografts was decreased by >80% in the mice treated with AEE788 alone and in combination with paclitaxel compared with the control group. Lastly, immunofluorescence microscopy showed the inhibition of EGFR autophosphorylation on the tumor cells as well as the inhibition of VEGFR-2 autophosphorylation on tumor endothelium. Considering the fact that curative options seldom exist for patients with ATC, concurrent inhibition of EGFR and VEGFR tyrosine kinases seems to be a valid and promising anticancer strategy for these patients.

Selenium supplementation may increase the efficacy of cetuximab in metastatic colorectal cancer patients.

Recently, cyclooxygenase-2 (COX-2) inhibitor therapy has emerged as a possible new approach to the prevention and treatment of colorectal cancer (CRC). The COX enzymes (COX-1 and COX-2) are key enzymes of prostaglandin (PG) biosynthesis and are overexpressed in approximately 80% of human CRCs. Presumably, bioactive lipid products of COX, such as PGE(2), are responsible for some of the pro-neoplastic effects mediated by this enzyme. The early effects of COX-2-derived PGE(2) are in part mediated by the epidermal growth factor receptor (EGFR). Selenomethionine decreases COX-2 protein and PGE(2) levels. Cetuximab is a chimeric IgG1 monoclonal antibody that binds to EGFR with high specificity thus blocking ligand-induced phosphorylation of EGFR. Cetuximab has clinically significant activity when given alone or in combination with irinotecan in patients with irinotecan-refractory CRC. We suggest that selenium supplementation by decreasing the COX-2 protein and PGE-2 levels in cancer cells may increase efficacy of cetuximab in advanced CRC patients.

AEE788, a dual tyrosine kinase receptor inhibitor, induces endothelial cell apoptosis in human cutaneous squamous cell carcinoma xenografts in nude mice.

PURPOSE: We investigated whether concomitant blockade of the epidermal growth factor receptor (EGFR) and vascular endothelial growth factor receptor (VEGFR) signaling pathways by AEE788, a dual inhibitor of EGFR and VEGFR tyrosine kinases, would inhibit the growth of cutaneous squamous cell carcinoma (SCC) cells and human cutaneous cancer xenografts in nude mice. EXPERIMENTAL DESIGN: We examined the effects of AEE788 on the phosphorylation of EGFR and VEGFR-2 in cutaneous SCC cells expressing EGFR and VEGFR-2 and cutaneous SCC cell growth and apoptosis. We assessed the in vivo antitumor effects of AEE788 in a xenograft model in nude mice. AEE788 (50 mg/kg) was given orally thrice weekly to mice that had been s.c. injected with Colo16 tumor cells. Mechanisms of in vivo AEE788 activity were determined by immunohistochemical analysis. RESULTS: Treatment of cutaneous SCC cells with AEE788 led to dose-dependent inhibition of EGFR and VEGFR-2 phosphorylation, growth inhibition, and induction of apoptosis. In mice treated with AEE788, tumor growth was inhibited by 54% at 21 days after the start of treatment compared with control mice (P < 0.01). Immunohistochemical analysis revealed that AEE788 inhibited phosphorylation of EGFR and VEGFR and induced apoptosis of tumor cells and tumor-associated endothelial cells. CONCLUSIONS: In addition to inhibiting cutaneous cancer cell growth by blocking EGFR and VEGFR signaling pathways in vitro, AEE788 inhibited in vivo tumor growth by inducing tumor and endothelial cell apoptosis.

Epidermal growth factor receptor (EGFR) is overexpressed in anaplastic thyroid cancer, and the EGFR inhibitor gefitinib inhibits the growth of anaplastic thyroid cancer.

PURPOSE: No effective treatment options currently are available to patients with anaplastic thyroid cancer (ATC), resulting in high mortality rates. Epidermal growth factor (EGF) has been shown to play a role in the pathogenesis of many types of cancer, and its receptor (EGFR) provides an attractive target for molecular therapy. EXPERIMENTAL DESIGN: The expression of EGFR was determined in ATC in vitro and in vivo and in human tissue arrays of ATC. We assessed the potential of the EGFR inhibitor gefitinib ("Iressa," ZD1839) to inhibit EGFR activation in vitro and in vivo, inhibit ATC cellular proliferation, induce apoptosis, and reduce the growth of ATC cells in vivo when administered alone and in combination with paclitaxel. RESULTS: EGFR was overexpressed in ATC cell lines in vitro and in vivo and in human ATC specimens. Activation of EGFR by EGF was blocked by the addition of gefitinib. In vitro studies showed that gefitinib greatly inhibited cellular proliferation and induced apoptosis in ATC cell lines and slowed tumor growth in a nude mouse model of thyroid carcinoma cells injected subcutaneously. CONCLUSIONS: ATC cells consistently overexpress EGFR, rendering this receptor a potential target for molecular therapy. Gefitinib effectively blocks activation of EGFR by EGF, inhibits ATC cellular proliferation, and induces apoptosis in vitro. Our in vivo results show that gefitinib has significant antitumor activity against ATC in a subcutaneous nude mouse tumor model and therefore is a potential candidate for human clinical trials.

Tumor cell and endothelial cell therapy of oral cancer by dual tyrosine kinase receptor blockade.

Expression of the epidermal growth factor (EGF) and activation of its receptor (EGFR), a tyrosine kinase, are associated with progressive growth of head and neck cancer. Expression of the vascular endothelial growth factor (VEGF) is associated with angiogenesis and progressive growth of tumor. The tyrosine kinase inhibitor NVP-AEE788 (AEE788) blocks the EGF and VEGF signaling pathways. We examined the effects of AEE788 administered alone, or with paclitaxel (Taxol), on the progression of human head and neck cancer implanted orthotopically into nude mice. Cells of two different human oral cancer lines, JMAR and MDA1986, were injected into the tongues of nude mice. Mice with established tumors were randomized to receive three times per week oral AEE788, once weekly injected paclitaxel, AEE788 plus paclitaxel, or placebo. Oral tumors were resected at necropsy. Kinase activity, cell proliferation, apoptosis, and mean vessel density were determined by immunohistochemical immunofluorescent staining. AEE788 inhibited cell growth, induced apoptosis, and reduced the phosphorylation of EGFR, VEGFR-2, AKT, and mitogen-activated protein kinase in both cell lines. Mice treated with AEE788 and AEE788 plus paclitaxel had decreased microvessel density, decreased proliferative index, and increased apoptosis. Hence, AEE788 inhibited tumor vascularization and growth and prolonged survival. Inhibition of EGFR and VEGFR phosphorylation by AEE788 effectively inhibits cellular proliferation of squamous cell carcinoma of the head and neck, induces apoptosis of tumor endothelial cells and tumor cells, and is well tolerated in mice. These data recommend the consideration of patients with head and neck cancer for inclusion in clinical trials of AEE788.

Ultrasonic decalcification of calcified valve and annulus during heart valve replacement.

A heavily calcified heart valve annulus increases the likelihood of sequelae after prosthetic valve replacement. Such sequelae include cerebral embolism, paravalvular leakage, valvular dysfunction, rhythm disturbance, hemolysis, communication of the heart chambers, and rupture of the posterior wall of the left ventricle. From January 1991 through June 1994, we performed heart valve replacement on 30 patients, using an ultrasonic surgical aspirator to remove calcific deposits. We placed aortic valve prostheses in 12 patients, mitral valve prostheses in 13 patients, and both aortic and mitral prostheses in 5 patients, after ultrasonic débridement of calcified annuli. All patients were re-examined 6 months after surgery: echocardiographic study showed no paravalvular leakage or valve-related complications. In our experience, ultrasonic decalcification of the annulus is superior to traditional methods. We advocate the use of ultrasonic débridement as an adjunctive tool in calcified heart valve replacement.

The effect of the male contraceptive agent gossypol acetic acid on mouse bone marrow cells in vivo: micronuclei and mitotic index.

In this work the genotoxic effect of gossypol acetic acid (gossypol) was evaluated by determining the frequency of micronuclei and mitotic index in male mouse bone marrow cells in vivo. Bone marrow cells were collected at 24th hour after the single intraperitoneal (20, 40, and 80 micrograms/g) administration of gossypol. Polychromatic erythrocytes (PCEs) in the bone marrow were then evaluated with respect to micronuclei frequency. The dose-dependent increase in the micronuclei frequency was observed. However, when compared with the control group, the increase was not found to be significant (P > 0.05). Also the mitotic index values were not found to be different from those control values (P > 0.05). The results suggest that gossypol is not a clastogenic and mutagenic agent in mouse bone marrow cells in vivo.